Visualization of Synovial Vascularization In a Preclinical Model of Arthritis Using [¹⁸F]Fluciclatide PET/CT: A Novel Integrin-Targeted Molecular Imaging Approach

Synovial angiogenesis is an early pathological hallmark of rheumatoid arthritis (RA) and contributes to pannus formation and joint destruction. Integrin αvβ3, overexpressed on activated endothelial cells, represents a promising molecular imaging target. In this study, we investigated whether [¹⁸F]Fluciclatide, a radiolabeled cyclic RGD peptide, enables non-invasive detection of αvβ3-mediated synovial angiogenesis in the antigen-induced arthritis (AIA) rat model, providing preclinical proof-of-concept for the tracer as a molecular imaging biomarker in RA. AIA was induced in male Wistar rats by intra-articular antigen injection, and integrin αvβ3 expression in knee joints was assessed by immunohistochemistry. Biodistribution studies and dynamic Positron Emission Tomography (PET) imaging were performed following intravenous administration of [¹⁸F]Fluciclatide, and the radiotracer specificity was evaluated using the αvβ3 antagonist Cilengitide. Arthritic knees demonstrated significantly increased αvβ3 expression compared with controls. Normalized tracer uptake was significantly higher in arthritic joints than in controls (2.47 ± 0.10 vs. 1.52 ± 0.11, p < 0.05) and was markedly reduced following Cilengitide blockade, confirming receptor-specific binding. Dynamic PET imaging showed approximately two-fold higher tracer accumulation in arthritic synovium compared with controls (SUVmean 1.86 ± 0.13 vs. 0.75 ± 0.06), with time-dependent uptake abolished after integrin receptor saturation. These findings show that [¹⁸F]Fluciclatide PET provides sensitive and specific imaging of synovial angiogenesis in the AIA rat model. The tracer’s high target-to-background contrast supports its potential as a non-invasive biomarker for early RA detection, patient stratification, and monitoring of anti-angiogenic therapies.